A11 ISOLATION OF NON-POLAR METABOLITES IN EXCRETORY/SECRETORY PRODUCTS FROM PARASITIC HELMINTHS AND THEIR POTENTIAL AS IMMUNOTHERAPY IN INFLAMMATORY BOWEL DISEASE
Notice bibliographique
Résumé
Abstract Background Parasitic helminths are known to modulate host immune responses. This is thought to be mediated by their secretome. We are interested in the excretory/secretory products and mechanisms for modulating immune dysfunction in autoinflammatory diseases. Aims This research studies the mechanisms of immune modulation by parasitic helminths in the context of IBD. We aim to describe immunomodulatory helminth-derived metabolites (ESM). Methods Helminth-conditioned media was used to isolate ESM, which were further purified using column chromatography. Bone marrow (BM) derived macrophages (BMDM) from C57BL6 mice, were treated with ESP fractions from Trichuris suis, Ascaris suum, Heligmosomoides polygyrus bakeri or Dirofilaria immitis, stimulated with LPS, and secreted cytokine levels measured. Moreover, BM was cultured with or without ESM throughout differentiation to BMDM. Colitic mice (3% DSS, 5 days) were treated with A. suum ESM or PBS once daily IP. Colon lengths and TNFα mRNA were measured, and histological preparations were scored to assess pathology. Bioactive D. immitis ESM were fractionated using preparatory HPLC and assayed for bioactivity. Active fractions were analysed using MS/MS and fragmentation patterns and molecular weights were obtained. The active fractions are currently being studied by NMR to deduce a structure of an active metabolite. Results BMDM treated with crude ESM decreased TNFα secretion and increased IL-10. BMDM precursors which were treated with A. suum ESM throughout differentiation had reduced proliferation in a dose dependent manner. These BMDM showed remodeling of BMDM metabolic pathways. Intracellular ROS production was inversely proportional to Alamar blue oxidation. We found that ESM from A. suum improved DSS-colitis. Specifically, mice with DSS-induced colitis given IP ESM had longer colons, lower histolopathology score, and lower TNFα mRNA expression in gut tissue. HPLC-fractionated D. immitis ESM used to treat BMDM yielded varying suppression of TNFα with LPS stimulation. MS/MS of TNFα suppressive fractions contained masses with fragmentation patterns which were detected in fractions of several of the above-mentioned parasite species. Preliminary NMR studies will determine if this represents a conserved structure. Conclusions Helminth-derived components can immunologically polarize a response in vitro, as well as favour recovery in DSS colitis. Through multiple purification steps, a nearly pure fraction is found to have bioactivity, suggesting a single, bioactive molecule that is conserved across several parasitic helminths. These data are important in understanding the host-parasite interaction modulated by ESM, as well as provide therapeutic potential in IBD. Funding Agencies NSERC, FRQNT
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».